EBF2 determines and maintains brown adipocyte identity

Sona Rajakumari, Jun Wu, Jeff Ishibashi, Hee Woong Lim, An Hoa Giang, Kyoung Jae Won, Randall R. Reed, Patrick Seale

Research output: Contribution to journalArticlepeer-review

Abstract

The master transcription factor Pparγ regulates the general differentiation program of both brown and white adipocytes. However, it has been unclear whether Pparγ also controls fat lineage-specific characteristics. Here, we show that early B cell factor-2 (Ebf2) regulates Pparγ binding activity to determine brown versus white adipocyte identity. The Ebf DNA-binding motif was highly enriched within brown adipose-specific Pparγ binding sites that we identified by genome-wide ChIP-Seq. Of the Ebf isoforms, Ebf2 was selectively expressed in brown relative to white adipocytes and was bound at brown adipose-specific Pparγ target genes. When expressed in myoblasts or white preadipose cells, Ebf2 recruited Pparγ to its brown-selective binding sites and reprogrammed cells to a brown fat fate. Brown adipose cells and tissue from Ebf2-deficient mice displayed a loss of brown-specific characteristics and thermogenic capacity. Together, these results identify Ebf2 as a key transcriptional regulator of brown fat cell fate and function.

Original languageEnglish (US)
Pages (from-to)562-574
Number of pages13
JournalCell Metabolism
Volume17
Issue number4
DOIs
StatePublished - Apr 2 2013

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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